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Direct Nanospectroscopic Verification of the Amyloid Aggregation Pathway
Author(s) -
Lipiec Ewelina,
PerezGuaita David,
Kaderli Janina,
Wood Bayden R.,
Zenobi Renato
Publication year - 2018
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201803234
Subject(s) - fibrillogenesis , fibril , raman spectroscopy , random coil , chemistry , monomer , protein aggregation , amyloid fibril , biophysics , nanotechnology , amyloid β , crystallography , materials science , biochemistry , biology , disease , polymer , circular dichroism , physics , organic chemistry , medicine , pathology , optics
The aggregation pathways of neurodegenerative peptides determine the disease etiology, and their better understanding can lead to strategies for early disease treatment. Previous research has allowed modelling of hypothetic aggregation pathways. However, their direct experimental observation has been elusive owing to methodological limitations. Herein, we demonstrate that nanoscale chemical mapping by tip‐enhanced Raman spectroscopy of single amyloid fibrils at various stages of aggregation captures the fibril formation process. We identify changes in TERS/Raman marker bands for Aβ 1‐42 , including the amide III band (above 1255 cm −1 for turns/random coil and below 1255 cm −1 for β‐sheet conformation). The spatial distribution of β‐sheets in aggregates is determined, allowing verification of a particular fibrillogenesis pathway, starting from aggregation of monomers to meta ‐stable oligomers, which then rearrange to ordered β‐sheets, already at the oligomeric or protofibrillar stage.